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Paper:4

  1. Title: A class of antibodies that overcome a steric barrier to cross-group neutralization of influenza viruses

  2. Authors: Holly C. Simmons, Akiko Watanabe, Thomas H. Oguin III, Gregory D. Sempowski, Masayuki Kuraoka, Garnett Kelsoe, and Kevin R. McCarthy

  3. Affiliation: Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

  4. Keywords: influenza virus, hemagglutinin, antibodies, cross-group neutralization, receptor binding site

  5. Urls: https://doi.org/10.1101/2023.04.01.535242, Github:None

  6. Summary:

  • (1): The research background of this paper is to find broadly protective antibodies to influenza viruses.
  • (2): Past methods have focused on targeting the hemagglutinin receptor binding site (RBS), but a steric barrier at position 133a on the RBS has prevented H1-H3 cross-subtype neutralization by RBS-targeted antibodies. The approach taken in this paper is well-motivated as the authors aim to identify a class of antibodies that can overcome this barrier.
  • (3): The research methodology proposed in this paper involves identifying a genetically unrestricted class of antibodies, which were likely elicited by exposure to H3 and then later broadened/diverted through exposure to H1 HA. They also analyze the affinities of selected members of this class for historical H1 and H3 isolates to determine the potential of eliciting 133a-independent, H1-H3 cross-neutralization by RBS-directed antibodies.
  • (4): The methods in this paper identified a class of antibodies that can overcome the steric barrier and showed that RBS mutations in egg-adapted vaccine strains cause the new H1 specificity of these antibodies to depend on the egg adaptation. The potential for suitable immunogens to elicit 133a-independent, H1-H3 cross-neutralization by RBS-directed antibodies is suggested. Thus, the results in this paper support the goal of finding broadly protective antibodies to influenza viruses.
  1. Conclusion:

  • (1): The significance of this work lies in the identification of a class of antibodies that can overcome a steric barrier in the hemagglutinin receptor binding site, leading to potential broad protection against different subtypes of influenza viruses.

  • (2): In terms of innovation, this article proposes a novel approach to identifying broadly protective antibodies by targeting a specific steric barrier, which is a significant contribution to the field. The performance of the methods is supported by the experimental results, which demonstrate the potential of the identified antibodies for cross-group neutralization. However, the workload required for the research is not explicitly discussed in the article. Overall, this article provides valuable insights into the development of broadly protective influenza vaccines.